Scientists Discover Master Regulator for Embryonic Stem Cells Researchers at the Genome Institute in Singapore, in collaboration with colleagues from the US, have discovered a gene that plays a crucial role in human embryonic stem cells. In a paper in the October issue of Nature Cell Biology,1 scientists studying mice identified a gene that encodes a transcription factor, Sall4, a protein that switches genes on or off. Such transcription factors are crucial for the identity of the cell, as they regulate which genes get expressed and when. As all cells in the body contain exactly the same genes, one of the challenges is the orchestration of proper regulation of genes particular for any given cell type. For example, a blood cell will require entirely different genes for its look and function than would a bone cell. Transcription factors also regulate the development of cells from the primitive stem cell stage to functional cells making up the tissue, and through the entire development from the fertilized egg to the grown individual. They also regulate the cell’s response to environmental changes. The transcription factor identified by these scientists functions during very early development and in embryonic stem cells. Sall4 is necessary to maintain embryonic stem cells in their undifferentiated state. In the developing embryo Sall4 participates in the very first decision about diverging cell lineages, the decision between making the embryo proper or the placenta. Mutations in only one copy of this gene (each human has two copies of his/her genes) causes an inherited disease which is characterized by limb and organ malformations. Mice with one mutated copy have similar defects and around 80% die before birth, whereas mice with mutations in both copies all die before birth. As this transcription factor seems to be a master switch controlling fate of embryonic stem cells, further study of Sall4 may shed insight into tissue engineering and the molecular processes needed to go from stem cells to differentiated cells and possibly back to stem cells. 1. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol. 2006 Oct;8(10):1114-23. Epub 2006 Sep 17. Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lufkin T, Robson P, Lim B. *Author affiliation: Posted October 16, 2006 Contact Friends of ISSCR | Privacy Statement | Disclaimer | ISSCR Home Page
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